Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells

The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans

A Morphological and Multicolor Survey for Faint QSOs in the Groth-Westphal Strip

Quasars representative of the populous faint end of the luminosity function are frustratingly dim with m~24 at intermediate redshift; moreover groundbased surveys for such faint QSOs suffer substantial morphological contamination by compact galaxies having similar colors. In order to establish a more reliable ultrafaint QSO sample, we used the APO 3.5-m telescope to take deep groundbased U-band CCD images in fields previously imaged in V,I with WFPC2/HST. Our approach hence combines multicolor photometry with the 0.1" spatial resolution of HST, to establish a morphological and multicolor survey for QSOs extending about 2 magnitudes fainter than most extant groundbased surveys. We present results for the "Groth-Westphal Strip", in which we identify 10 high likelihood UV-excess candidates having stellar or stellar-nucleus+galaxy morphology in WFPC2. For m(606)<24.0 (roughly B<24.5) the surface density of such QSO candidates is 420 (+180,-130) per square degree, or a surface density of 290 (+160,-110) per square degree with an additional V-I cut that may further exclude compact emission line galaxies. Even pending confirming spectroscopy, the observed surface density of QSO candidates is already low enough to yield interesting comparisons: our measures agree extremely well with the predictions of several recent luminosity function models.Comment: 29 pages including 6 tables and 7 figures. As accepted for publication in The Astronomical Journal (minor revisions

Converting Pairing-Based Cryptosystems from Composite-Order Groups to Prime-Order Groups

We develop an abstract framework that encompasses the key properties of bilinear groups of composite order that are required to construct secure pairing-based cryptosystems, and we show how to use prime-order elliptic curve groups to construct bilinear groups with the same properties. In particular, we define a generalized version of the subgroup decision problem and give explicit constructions of bilinear groups in which the generalized subgroup decision assumption follows from the decision Diffie-Hellman assumption, the decision linear assumption, and/or related assumptions in prime-order groups. We apply our framework and our prime-order group constructions to create more efficient versions of cryptosystems that originally required composite-order groups. Specifically, we consider the Boneh-Goh-Nissim encryption scheme, the Boneh-Sahai-Waters traitor tracing system, and the Katz-Sahai-Waters attribute-based encryption scheme. We give a security theorem for the prime-order group instantiation of each system, using assumptions of comparable complexity to those used in the composite-order setting. Our conversion of the last two systems to prime-order groups answers a problem posed by Groth and Sahai

Warm dark matter at small scales: peculiar velocities and phase space density

We study the scale and redshift dependence of the power spectra for density perturbations and peculiar velocities, and the evolution of a coarse grained phase space density for (WDM) particles that decoupled during the radiation dominated stage. The (WDM) corrections are obtained in a perturbative expansion valid in the range of redshifts at which N-body simulations set up initial conditions, and for a wide range of scales. The redshift dependence is determined by the kurtosis $\beta_2$ of the distribution function at decoupling. At large redshift there is an enhancement of peculiar velocities for $\beta_2 > 1$ that contributes to free streaming and leads to further suppression of the matter power spectrum and an enhancement of the peculiar velocity autocorrelation function at scales smaller than the free streaming scale. Statistical fluctuations of peculiar velocities are also suppressed on these scales by the same effect. In the linearized approximation, the coarse grained phase space density features redshift dependent (WDM) corrections from gravitational perturbations determined by the power spectrum of density perturbations and $\beta_2$. For $\beta_2 > 25/21$ it \emph{grows logarithmically} with the scale factor as a consequence of the suppression of statistical fluctuations. Two specific models for WDM are studied in detail. The (WDM) corrections relax the bounds on the mass.Comment: 22 pages, 9 figs, more explanations. Published versio

Snarky Signatures: Minimal Signatures of Knowledge from Simulation-Extractable SNARKs

We construct a pairing based simulation-extractable SNARK (SE-SNARK) that consists of only 3 group elements and has highly efficient verification. By formally linking SE-SNARKs to signatures of knowledge, we then obtain a succinct signature of knowledge consisting of only 3 group elements. SE-SNARKs enable a prover to give a proof that they know a witness to an instance in a manner which is: (1) succinct - proofs are short and verifier computation is small; (2) zero-knowledge - proofs do not reveal the witness; (3) simulation-extractable - it is only possible to prove instances to which you know a witness, even when you have already seen a number of simulated proofs. We also prove that any pairing based signature of knowledge or SE-NIZK argument must have at least 3 group elements and 2 verification equations. Since our constructions match these lower bounds, we have the smallest size signature of knowledge and the smallest size SE-SNARK possible

A thermostable enzyme as an experimental platform to study properties of less stable homologues.

The structural and functional characterization of proteins is frequently hampered by lack of stability or by insufficient assembly of oligomeric proteins in over-expression systems. Using

Disorder-Induced Multiple Transition involving Z2 Topological Insulator

Effects of disorder on two-dimensional Z2 topological insulator are studied numerically by the transfer matrix method. Based on the scaling analysis, the phase diagram is derived for a model of HgTe quantum well as a function of disorder strength and magnitude of the energy gap. In the presence of sz non-conserving spin-orbit coupling, a finite metallic region is found that partitions the two topologically distinct insulating phases. As disorder increases, a narrow-gap topologically trivial insulator undergoes a series of transitions; first to metal, second to topological insulator, third to metal, and finally back to trivial insulator. We show that this multiple transition is a consequence of two disorder effects; renormalization of the band gap, and Anderson localization. The metallic region found in the scaling analysis corresponds roughly to the region of finite density of states at the Fermi level evaluated in the self-consistent Born approximation.Comment: 5 pages, 5 figure